Clinical Evidence Concise
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Am Fam Physician. 2006 May 1;73(9):1611-1614.
This clinical content conforms to AAFP criteria for evidence-based continuing medical education (EB CME). EB CME is clinical content presented with practice recommendations supported by evidence that has been systematically reviewed by an AAFP-approved source. The evidence is available at http://www.clinicalevidence.com/ceweb/conditions/chd/0305/0305.jsp.
What are the effects of interventions for the relief of symptoms?
Enuresis Alarm. One systematic review showed that an enuresis alarm decreased the number of wet nights during treatment and increased treatment success rates at 10 to 20 weeks compared with no treatment. One review showed no significant difference between enuresis alarms and dry-bed training in treatment success rates at four to 20 weeks. The review showed that an alarm combined with dry-bed training increased treatment success and reduced relapse at eight to 20 weeks compared with no treatment. There were no significant differences between an alarm plus dry-bed training and an alarm alone in treatment success or in relapse rates after discontinuing treatment.
Another systematic review showed no significant difference between desmopressin and an enuresis alarm in the number of children who achieved initial success. However, it showed limited evidence that desmopressin reduced wet nights compared with an alarm during the first week of treatment. A subsequent randomized controlled trial (RCT) showed that desmopressin significantly reduced wet nights during 12 weeks of treatment compared with an alarm. One systematic review showed that desmopressin plus an alarm reduced the number of wet nights per week during treatment compared with an alarm alone or an alarm plus placebo. However, there was no significant difference between an alarm plus desmopressin and an alarm alone in treatment success rates (defined as 14 consecutive dry nights) after six to 24 weeks or in relapse rates after treatment discontinuation.
RCTs showed that enuresis alarms reduced treatment failure and relapse rates after treatment discontinuation at eight to 14 weeks compared with tricyclic drugs. One RCT showed that there was no evidence that an enuresis alarm was more effective after five to six weeks when combined with tricyclic drugs.
Dry-Bed Training Plus Enuresis Alarm. Adding an enuresis alarm to dry-bed training increased treatment success rates and decreased relapse rates.
Desmopressin (While Treatment Continues). One systematic review showed that desmopressin decreased wet nights and increased initial treatment success compared with placebo. The review showed insufficient evidence comparing intranasal with oral desmopressin or desmopressin with tricyclic drugs. There was limited evidence that higher doses of desmopressin decreased wet nights during treatment compared with lower doses. One systematic review showed insufficient evidence comparing desmopressin with tricyclic drugs. The review showed no significant difference between desmopressin and an enuresis alarm in the numberof children achieving initial success. However, it showed limited evidence that desmopressin reduced wet nights compared with an alarm during the first week of treatment.
A subsequent RCT showed that desmopressin reduced wet nights during 12 weeks of treatment compared with an alarm. One RCT showed no significant difference between laser acupuncture and intranasal desmopressin in the number of wet nights after three months. We found no RCTs comparing the effects of adding desmopressin to the anticholinergic drugs oxybutynin, tolterodine, and hyoscyamine.
TRADE-OFF BETWEEN BENEFITS AND HARMS
Tricyclic Drugs (Imipramine, Desipramine). One systematic review showed that the use of tricyclic drugs (imipramine, desipramine) increased treatment success rates compared with placebo, although this benefit did not continue after treatment discontinuation. Tricyclic drugs are associated with adverse effects (anorexia, anxiety, constipation, depression, diarrhea, dizziness, drowsiness, dry mouth, headache, irritability, lethargy, sleep disturbance, upset stomach, vomiting) compared with placebo.
RCTs showed that an enuresis alarm reduced treatment failure and relapse after treatment discontinuation at eight to 14 weeks compared with tricyclic drugs. One RCT showed no evidence that an enuresis alarm was more effective after five to six weeks when combined with tricyclic drugs. One systematic review showed insufficient evidence comparing desmopressin with tricyclic drugs. One small RCT showed that a combination of oxybutynin and imipramine increased treatment success compared with placebo.
UNLIKELY TO BE BENEFICIAL
Desmopressin (After Treatment Discontinuation). Small RCTs showed limited evidence that there was no significant difference between desmopressin and placebo in treatment success rates after treatment discontinuation. Two RCTs showed that desmopressin was less effective than alarms when treatment ended.
Standard Home Alarm Clock. One RCT showed that more children using standard home alarm clocks achieved 14 consecutive dry nights during four months of treatment compared with those who were awakened every three hours; however, it showed no significant difference in relapse rates three months after treatment discontinuation.
Dry-Bed Training. One systematic review showed insufficient evidence to determine whether dry-bed training alone for eight to 24 weeks was superior to no intervention. The review showed that an enuresis alarm increased dry nights at four to 20 weeks compared with dry-bed training alone.
Desmopressin Plus Enuresis Alarm. One systematic review showed that desmopressin plus an enuresis alarm reduced the number of wet nights per week during initial treatment compared with the alarm alone or the alarm plus placebo. However, there was no significant difference between the alarm plus desmopressin and the alarm alone in treatment success rates at six to 24 weeks or in relapse rates after treatment discontinuation.
Anticholinergic Drugs (Oxybutynin, Tolterodine, Hyoscyamine). One small RCT provided insufficient evidence to determine the effectiveness of the anticholinergic drugs oxybutynin, tolterodine, and hyoscyamine for the treatment of nocturnal enuresis. We found no RCTs comparing oxybutynin, tolterodine, and hyoscyamine with desmopressin, tricyclic drugs, alarms, or dry-bed training. One small RCT showed that combining oxybutynin and imipramine (a tricyclic drug) increased treatment success rates compared with placebo.
Laser Acupuncture (as Effective as Desmopressin In One RCT). One RCT showed no significant difference between laser acupuncture and intranasal desmopressin in the number of wet nights after three months.
Nocturnal enuresis is the involuntary discharge of urine at night in a child five years or older who does not have congenital or acquired defects of the central nervous system or urinary tract.1 Disorders that are associated with bed-wetting (e.g., nocturnal incontinence) can be excluded with a thorough history, examination, and urinalysis. Monosymptomatic nocturnal enuresis only occurs at night and accounts for 85 percent of cases. Nocturnal enuresis is defined as primary if the child has not had a dry night for more than six months and as secondary if a period of dryness preceded the onset of bed-wetting. Most management strategies are aimed at children who are seven years or older.
On average, 15 to 20 percent of five-year-olds, 7 percent of seven-year-olds, 5 percent of 10-year-olds, 2 to 3 percent of 12- to 14-year-olds, and 1 to 2 percent of persons 15 years or older wet the bed twice per week.2
Nocturnal enuresis is associated with several factors including small functional bladder capacity; nocturnal polyuria; and, most commonly, arousal dysfunction. Linkage studies have identified associated genetic loci on chromosomes 8q, 12q, 13q, and 22q11.3–6
Nocturnal enuresis has widely differing outcomes, from spontaneous resolution to complete resistance to treatment. About 1 per cent of children remain enuretic until adulthood. Without treatment, about 15 percent of children with enuresis stop wetting the bed each year.7 We found no RCTs on the best age at which to start treatment in children with nocturnal enuresis. Behavioral treatments (e.g., moisture or wetting alarms) require motivation and commitment from the child and a parent. Anecdotal experience suggests that reassurance is sufficient for children younger than seven years, because these children may not exhibit the commitment needed.
search date: March 2005
Adapted with permission from Makari J, Rushton HG. Nocturnal enuresis. Clin Evid Concise 2006; 15:117–9.
1. Forsythe WI, Butler R. 50 years of enuretic alarms; a review of the literature. Arch Dis Child. 1991;64:879–85.
2. Blackwell C. A guide to enuresis: a guide to treatment of enuresis for professionals. Bristol: Eric, 1989.
3. Eiberg H. Total genome scan analysis in a single extended family for primary nocturnal enuresis: evidence for a new locus (ENUR 3) for primary nocturnal enuresis on chromosome 22q11 Eur Urol. 1998;33:34–6.
4. Eiberg H. Nocturnal enuresis is linked to a specific gene. Scand J Urol Nephrol. 1995;173(suppl):S15–7.
5. Arnell H, Hjalmas M, Jagervall G, et al. The genetics of primary nocturnal enuresis: inheritance and suggestion of a second major gene on chromosome 12q. J Med Genet. 1997;34:360–5.
6. Eiberg H, Berendt I, Mohr J. Assignment of dominant inherited nocturnal enuresis (ENUR 1) to chromosome 13q. Nat Genet. 1995;10:354–6.
7. Forsythe WI, Redmond A. Enuresis and spontaneous cure rate of 1129 enuretics. Arch Dis Child. 1974;49:259–63.
This is one in a series of chapters excerpted from Clinical Evidence Concise, published by the BMJ Publishing Group, Tavistock Square, London, United Kingdom. Clinical Evidence Concise is published in print twice a year and is updated monthly online. Each topic is revised every 12 months, and subscribers should view the most up-to-date version at http://www.clinicalevidence.com. If you are interested in contributing to Clinical Evidence, please send an e-mail to CEcommissioning@bmj.com. This series is part of the AFP's CME. See “Clinical Quiz” on page 1509.
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